Applications of Cell-Based Protein Array Technology to Preclinical Safety Assessment of Biological Products.

Off-target evaluation is essential in preclinical safety assessments of novel biotherapeutics, supporting lead molecule selection, endpoint selection in toxicology studies, and regulatory requirements for first-in-human trials. Off-target interaction of a therapeutic antibody and antibody derivatives has been historically assessed via the Tissue Cross-Reactivity (TCR) study, in which the candidate molecule is used as a reagent in immunohistochemistry (IHC) to assess binding of the candidate molecule to a panel of human tissue sections. The TCR approach is limited by the performance of the therapeutic as an IHC reagent, which is often suboptimal to outright infeasible.

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions.

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cell's transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors.

Early childhood educators' perspectives of the social functioning and strengths of children exposed to intimate partner violence.

Background: Exposure to IPV can negatively impact children's social functioning. However, children exposed to IPV can also display significant strengths. The early educational environment can be a key factor promoting resilience outside of the family, with early educators in an ideal position to identify a broad range of social challenges, strengths and needs of children exposed to IPV.

The INGENIOUS project: towards understanding air pollution in homes.

This paper provides an overview of the INGENIOUS (UnderstandING the sourcEs, traNsformations and fates of IndOor air pollUtantS) project, aiming to better understand air pollution in homes. Although our homes are the microenvironment in which we spend most of our time, we know relatively little about the sources, transformation processes and fates of indoor air pollutants, or our exposure to them. INGENIOUS aims to address this knowledge gap by delivering: an indoor emissions inventory for UK homes; comprehensive air pollutant measurements in 310 homes in Bradford using a combination of low cost-sensors and more advanced air quality instrumentation; an analysis of the impact of indoor air pollution on outdoor air quality and using mobile measurements; insight into future indoor air quality using detailed air pollution models; identification of indoor air pollutants that warrant further toxicological study; and better understanding of the barriers and facilitators for behaviour that drives improved indoor air quality.

Frequent, heterogenous fire supports a forest owl assemblage.

Fire shapes biodiversity in many forested ecosystems, but historical management practices and anthropogenic climate change have led to larger, more severe fires that threaten many animal species where such disturbances do not occur naturally. As predators, owls can play important ecological roles in biological communities, but how changing fire regimes affect individual species and species assemblages is largely unknown. Here, we examined the impact of fire severity, history, and configuration over the past 35 years on an assemblage of six forest owl species in the Sierra Nevada, California, using ecosystem-scale passive acoustic monitoring.